A method called an MS/MS analysis (or tandem analysis) is widely used as one of the mass spectrometric techniques for identification, structural analyses or quantitative determination of compounds having large molecular weights. There are various kinds of mass spectrometers with different configurations designed for the MS/MS analysis, among which tandem quadrupole mass spectrometers are characterized by their relatively simple structure as well as easy operation and handling.
In a generally used tandem quadrupole mass spectrometer, ions generated from a sample in an ion source are introduced into a first quadrupole mass filter (which is often represented as “Q1”), in which an ion having a specific mass-to-charge ratio (m/z) is selected as a precursor ion. This precursor ion is introduced into a collision cell containing an ion guide with four or more poles (this ion guide is commonly represented as “q2”). A collision-induced dissociation (CID) gas, such as argon, is supplied to this collision cell, and the precursor ion in the collision cell collides with this CID gas, to be fragmented into various kinds of product ions. These product ions are introduced into a second quadrupole mass filter (which is often represented as “Q3”), which selectively allows a product ion having a specific mass-to-charge ratio (m/z) to pass through it and reach a detector, to be thereby detected.
The tandem quadrupole mass spectrometer can be used independently. However, this device is often coupled with a chromatograph, such as a gas chromatograph (GC) or liquid chromatograph (LC). In recent years, chromatograph tandem quadrupole mass spectrometers have become vital devices in the field of analyzing a trace amount of sample containing a large amount of compounds or contaminated with various impurities, such as testing residual pesticides in foodstuffs, testing environmental pollutants, checking the concentration of medicinal chemicals in blood, or screening drugs or poisonous substances.
MS/MS analyses by chromatograph tandem quadrupole mass spectrometers can be conducted in various measurement modes, such as a multiple reaction monitoring (MRM) mode, precursor-ion scan mode, product-ion scan mode, and neutral-loss scan mode (see Patent Document 1). In the MRM mode, the mass-to-charge ratio at which ions are allowed to pass through is fixed in each of the first and second quadrupole mass filters so as to fragment a specific kind of precursor ion and measure an intensity (or amount) of a specific kind of product ion resulting from the fragmentation. The two-stage mass filtering in the MRM measurement eliminates unwanted components other than those to be analyzed, ions originating from impurities, and neutral particles, so that an ion intensity signal with high signal-to-noise ratio can be obtained. Due to this feature, the MRM measurement is particularly effective for the quantitative analysis of a trace amount of component. For example, gas chromatograph tandem mass spectrometers (GC/MS/MS) are frequently operated in the MRM mode to perform a simultaneous multi-component quantitative analysis of residual pesticides, which requires determining the quantity of an extremely small amount of components.
The chromatograph tandem mass spectrometer can also be operated similarly to a chromatograph mass spectrometer having only one quadrupole mass filter to perform a scan measurement or selected ion monitoring (SIM) measurement, neither of which involves the dissociation of ions. For example, it can be operated in a Q1SIM mode or Q1 scan mode, in which case the ion selection is performed in the first quadrupole mass filter while ions are allowed to pass through the second quadrupole mass filter, as well as in a Q3SIM mode or Q3 scan mode, in which case all the ions are initially allowed to pass through the first quadrupole mass filter, and subsequently, undergo the selection process by the second quadrupole mass filter. A Q3SIM mode is frequently used for a quantitative analysis of known kinds of compounds which have a relatively low molecular weight and are less likely to yield characteristic product ions.
In a chromatograph quadrupole mass spectrometer or a tandem version of the same device, various components in a sample are temporally separated in the chromatograph. However, if the sample contains too many compounds of interest, the chromatograph cannot adequately separate them, allowing two or more compounds to overlap each other and be introduced into the mass spectrometer in almost the same range of time. To address this problem, this type of mass spectrometer conventionally has the capability of alternately performing Q3SIM and MRM measurements for multiple ions of different mass-to-charge ratios within the same range of time to obtain an ion-intensity signal originating from each of the different compounds.
For convenience of user setting of the measurement conditions of such a complex measurement, the following method has been adopted in the conventional chromatograph quadrupole mass spectrometer:
Each measurement mode to be performed and the measurement conditions for that measurement mode (e.g. for the MRM mode, the conditions include the m/z values to be selected by the first quadrupole mass filter and the m/z values to be selected by the second quadrupole mass filter) are specified as “events.” If a plurality of events are specified for a certain range of time, a set of analyses are sequentially and cyclically repeated, with each analysis being conducted according to the conditions specified in one of the plurality of events. In the case of a quantitative analysis by an SIM or MRM measurement, each event basically corresponds to one of the compounds to be analyzed, because the content of each event is determined so as to analyze an ion or ions having mass-to-charge ratios characteristic of the target compound.
In this method, since a plurality of measurements are sequentially performed according to the events, setting a larger number of events to the same range of time leads to a shorter period of time assigned to each measurement or a longer interval of time for the repetition of the same event. In the former case, the accuracy and sensitivity of the measurement will deteriorate, which leads to a decrease in the accuracy of the quantitative determination. The latter case has the possibility of overlooking a maximum value of the component concentration, i.e. a peak top on the chromatogram, which deteriorates the accuracy of the peak area and similarly leads to a decrease in the accuracy of the quantitative determination. To avoid these situations, the range of time from the beginning (sample injection) to the end of the analysis is divided into a plurality of time units called “segments”, or a plurality of segments which do not overlap each other are set within the range of time from the beginning to the end of the analysis, and the events are set for each segment.
FIG. 5 is a chart showing the concept of setting segments and events with respect to the elapse of time. The segments may be specified continuously (as in the case of segments #1 through #3 in the figure) or discontinuously (as in the case of segments #3 and #4) on the time axis. In most cases, users choose the continuous setting of the segments. Each segment has one or more events allotted thereto. For example, during the period of time from t1 to t2, for which segment #1 is set, two measurements according to the two events, i.e. events #1 and #2, will be repeated. By this method, for each compound to be analyzed, users only need to specify the events for the quantitative determination in one or more segments around the retention time of the compound in question. It is unnecessary to allot many events to each and every event.
As already explained, in the case of using events and segments to set measurement conditions, allotting a smaller number of events to one segment provides a higher accuracy of the chromatogram. The reduction of the number of events can be achieved by decreasing the time span of the segments and setting the segments at smaller intervals in accordance with the retention times of the compounds to be analyzed. However, it is often the case that a compound to be analyzed appears at a point in time displaced from the expected retention time due to a change in the condition of the chromatographic separation or other factors. Therefore, if the time span of the segments is reduced, a peak which characterizes the target compound on the chromatogram will probably appear across the boundary of the segments, without being included in one segment.
In conventional devices, in the case where a chromatogram peak lies across the boundary of two or more segments, if the same measurement mode with the same measurement conditions is allotted to the same event number in any of these segments, the obtained partial chromatograms can be connected across the segments to draw a continuous peak curve. However, even when the mode and conditions of the measurements are the same, if the event number is different, the resultant chromatogram will have a missing portion at the boundary of the segments, as shown in FIG. 4A. Consequently, for a chromatogram with a peak lying on two or more segments, it is impossible to correctly perform the peak-waveform processing and determine the correct peak area. Such a situation often results in a significant deterioration in the reliability of the quantitative determination or an unsuccessful identification of a component.
To avoid such a situation, analysis operators (users) need to determine whether the leading or tailing portion of a peak is likely to appear across the boundary of the segments, and if this situation is expected, they need to appropriately arrange the condition setting so that all the events with the same measurement mode and the same measurement conditions will have the same event number. This task is cumbersome and puts a heavy workload on the operators. Furthermore, such a task is likely to cause users to make some mistakes, thus constituting a major cause of an incorrect result of the analysis.